EBV-immortalized B cells die when incubated at sufficiently low cell densities. Cell death occurs via apoptosis and is prevented by addition of IL-6 or lactic acid to the culture medium. We have examined the process of cell death in EBV immortalized cells and have concluded that a deregulated c-myc in EBV-immortalized B cells is critical to the induction of apoptosis following growth factor deprivation. Deregulated c-myc is also characteristic of B cells derived from Burkitt's lymphoma (BL) biopsies but BL cells are generally more resistant to apoptosis induced by growth factor starvation or irradiation. In contrast to EBV immortalized B cells, BL cells frequently exhibit mutations in the p53 tumor suppressor gene suggesting wt p53 function is critical for the apoptotic response. However, inactivation of p53 function in an EBV immortalized cell line did not alter it's response to factor starvation or gamma irradiation, while inactivation of p53 function in a BL cell line which also carries a mutant p53 protein, render the cell line resistant to the induction of apoptosis, suggesting that the presence of mutant p53 is crucial. We have also utilized an in vivo athymic mouse model to test the in vivo growth potential of B cells varying in their p53 status. Using an in vitro assay that measures p53-dependent cell cycle arrest in the G1 phase of cell cycle, a highly significant correlation was found between the ability of BL cells to arrest in G1 after irradiation and their tumorigenicity in athymic mice. Transfection of wt p53 gene into the p53 mutant and highly tumorigenic BL41 cell line caused it to acquire wt p53 function and rendered it non-tumorigenic in mice. Inactivation of wild-type p53 function in a non tumorigenic BL cell line which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in athymic mice. However, inactivation of wild-type p53 function in the non-tumorigenic EBV-immortalized cells did not alter their in vivo growth potential. Although tentative, these results suggest that mutations in p53 specifically enhance tumorigenicity by providing a selective growth advantage in vivo.